Substance misuse is the leading preventable cause of morbidity and mortality in females. Effective prevention of substance misuse by females, depends, in part on increased understanding of femalespecific risk and protective factors that influence pathways toward and away from addiction. The main goal of the proposed research, which directly addresses NIDA strategic priorities in prevention, is to investigate factors influencing the development of substance use, abuse, and dependence in girls during a period of peak risk (ages 15-22). This renewal requests continuation of NIDA support for 5 further annual substance use assessments (i.e., Years 11-15) with girls and their parent as a substudy to the NIMH-funded Pittsburgh Girls Study (PGS; N = 2,451; 52% African American, 41% Caucasian), a longitudinal, population-based study of the development of conduct problems and depression in four cohorts of girls, initially assessed at ages 5 to 8. The next 5 years, which will cover ages 15-22 in an accelerated longitudinal design, are critical to understanding factors influencing the development of substance use and HIV risk behaviors (e.g., risky sexual behavior) during adolescence and the transition to young adulthood. The proposed project aims to: (1) characterize trajectories of substance use, abuse, and dependence in girls, starting in childhood, through adolescence, and into emerging adulthood; (2) examine trajectories of girls substance involvement in conjunction with the developmental course of psychopathology (e.g., depression) and other problem behaviors (e.g., risky sexual behavior); (3) determine how proximal and distal risk and protective factors (both general and female-specific) influence the development of substance involvement in girls, including analyses of differences by ethnicity; and (4) to simultaneously examine trajectories of substance use and HIV risk behaviors to determine how these health compromising behaviors interact over time to influence HIV risk in females. The proposed continuation of 5 annual substance use assessments, in conjunction with 10 waves of data already collected, will permit the linkage of childhood factors to substance use and HIV risk behaviors during adolescence and emerging adulthood. The PGS, as one of very few population-based studies of females in the US, is uniquely suited to addressing gaps in knowledge regarding the ways in which individual, environmental, and developmental factors interact to influence substance use in a large, urban sample of African American and Caucasian girls. Study findings will be used to improve substance use and HIV risk screening, and to guide prevention efforts for females.